The effects of cyclosporin A (CsA) on T lymphocyte development was investigated in the mouse by exposing fetal thymic organ cultures (FTOC) to CsA, and subsequently assessing T cell developmental markers by flow cytometry. CsA inhibited: a) the maturation of single positive (CD4+CD8- and CD4-CD8+) thymocytes; and b) the development of double positive from double negative thymocytes. The stimulation of human T helper cells (Th) in vitro with recall antigens, HLA alloantigens, and mitogens in the presence of different doses of CsA resulted the selective dose-dependent loss of recall responses. This pattern of unresponsiveness resembles the loss of Th seen in AIDS development. Such results: a) led to the demonstration of three distinct Th pathways in human peripheral blood leukocytes (PBL) which has been valuable in interpreting results in AIDS patients; b) initiated a study of Th analyses in renal allografted patients, with the result that kidney graft rejection could be predicted, by in vitro testing of Th pathways of PBL from the transplanted patients.